INIMIN – Boosting natural defence against the flu

EU-funded research has revealed for the first time in detail how people's immune systems react to vaccination. The discovery paves the way for more powerful vaccines to help vulnerable groups, in particular, fight annual bouts of influenza. The results could one day save thousands of lives and millions of euros in health-care costs.

Vaccination is a proven way of persuading the immune system to protect the body against crafty viral infections such as influenza. But until very recently, surprisingly little was known about how the body's innate defences actually work their magic.

With the support of a multi-disciplinary research team made up of scientists from Harvard Medical School and Dana Farber Cancer Institute – both in the USA – Spanish researcher Santiago Fernández González has revealed in great detail how a person's immune system reacts to vaccination.

Flu vaccinations basically contain a weakened or 'deactivated' form of the virus which tricks the body into believing it is under attack. The immune system's reaction leads to the creation of antibodies which are then already programmed to defend a person in the event of a full-blown infection.

The virus contained in the vaccine is first identified and surrounded by some specific cells – 'medullary dendritic' – found in the lymph node, notes Dr González. He has just returned to Europe following a Marie Curie fellowship organised through the Centro Nacional de Biotecnología, Spain. These cells effectively escort the virus to the lymphocytes – the cells that eventually produce antibodies that will fight the virus.

Dr González used new imaging techniques pioneered by Harvard Medical School to see what happens inside the lymph node by following the cells' movement and interaction in live tissues. Findings related to this were published in the Nature Immunology journal in 2010.

The Marie Curie fellow is now investigating if the same mechanisms exist when analysing 'live' viral infections (in vivo studies). "This work could help to minimise the damage caused by influenza infection in people who were not previously vaccinated," Dr González explains.
The quest for long-lasting immunity
With support from the EU-funded project Defence mechanisms of innate immunity against influenza virus (INIMIN), Dr González and associates have discovered the role of specific proteins and receptors (that act like a check-in desk) in the development of 'memory B cells' in the lymph node which recognise the virus. Proteins are important molecules that our bodies and the cells in our bodies need to function properly.

"The first line of defence against infection is the innate system which is non-specific and tends to offer only short-term immunity," says Dr González. So he studied ways of boosting this immunity with the help of a small number of proteins largely produced in the liver that 'complement' the body's innate defence.

"Until recently, relatively little was known about the interaction of this 'complementary system' and infectious agents like influenza which, as it mutates, poses a major threat to health every year," says the young scientist who is currently group leader responsible for the infection and immunity lab at the Institute of Research for Biomedicine, Switzerland.

Armed with this knowledge, his plan is to lengthen the memory response so that our immune system could recognise the new variants of the virus. This could save thousands of lives and many millions of euros in health costs every year, he suggests.

Funding for INIMIN has helped Dr González and his colleagues to discover how the body's protective response against influenza virus is initiated. Knowing how flu vaccines actually work is critical to developing more efficient therapies to strengthen the protective response against the virus.

"This is especially relevant for vulnerable groups, such as the elderly, infants and people with compromised immune systems, where the efficiency of the vaccine is limited," he stresses.